Codon 129 Polymorphism Specific Cerebrospinal Fluid Proteome Pattern in Sporadic Creutzfeldt−Jakob Disease and the Implication of Glycolytic Enzymes in Prion-Induced Pathology

2010 ◽  
Vol 9 (11) ◽  
pp. 5646-5657 ◽  
Author(s):  
Joanna Gawinecka ◽  
Jana Dieks ◽  
Abdul R. Asif ◽  
Julie Carimalo ◽  
Uta Heinemann ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Glycolytic Enzymes ◽  
Jakob Disease ◽  
Codon 129

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

2017 ◽  
Vol 43 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Franc Llorens ◽  
André Karch ◽  
Ewa Golanska ◽  
Matthias Schmitz ◽  
Peter Lange ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Negative Correlation ◽  
Disease Duration ◽  
Population Sample ◽  
Clinical Accuracy ◽  
Jakob Disease ◽  
And Control ◽  
Fluid Biomarker ◽  
Prnp Codon ◽  
Codon 129

Background: Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions. Methods: We analyzed 14-3-3, tau, p-tau levels, and the p-tau/tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs. Additionally, the correlation between biomarkers and disease duration as well as the influence of the PRNP129 polymorphism are reported. Results: The tau levels and p-tau/tau ratios differed considerably between sCJD and clinically characterized non-CJD cases (p < 0.001). p-tau was only elevated in sCJD when compared to cases without dementia (p < 0.05). Tau and the p-tau/tau ratio showed a sensitivity of 95 and 100%, respectively, in detecting sCJD cases. A negative correlation between tau levels and disease duration, but not the timing of lumbar puncture was observed. Conclusion: The present findings confirmed the value of the p-tau/tau ratio as a robust sCJD biomarker and suggest a role for tau as prognostic marker.

scholarly journals Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

2021 ◽  
Vol 22 (4) ◽  
pp. 2099
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Radoslav Matej
Keyword(s):  
Prion Protein ◽  
Fluorescent Microscopy ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Key Characteristics ◽  
Jakob Disease ◽  
Immunohistochemical Methods ◽  
Confocal Fluorescent Microscopy ◽  
Codon 129

Alzheimer’s disease (AD) and sporadic Creutzfeldt–Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins—amyloid β-protein (Aβ) and prion protein (PrPSc), respectively. To investigate the potential morphological colocalization of Aβ and PrPSc aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrPSc aggregates tended to be, in most cases, located separately, and “compound” plaques were relatively rare. We observed PrPSc plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer’s association guidelines, and prion protein subtype with codon 129 methionine–valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrPSc co-aggregates. However, our data showed that PrPSc aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.

scholarly journals Atypical Creutzfeldt-Jakob Disease Evolution after Electroconvulsive Therapy for Catatonic Depression

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Iria Grande ◽  
Juan Fortea ◽  
Ellen Gelpi ◽  
Itziar Flamarique ◽  
Marc Udina ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Disease Duration ◽  
Psychiatric Symptoms ◽  
Psychiatric Admission ◽  
Disease Evolution ◽  
Clinical Recovery ◽  
Jakob Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Electroencephalogram Eeg ◽  
Codon 129

We describe a case report of an 80-year-old woman who presented with symptomatology compatible with an episode of major depression with catatonia. After psychiatric admission, electroconvulsive therapy (ECT) was applied, but symptoms progressed with cognitive impairment, bradykinesia, widespread stiffness, postural tremor, and gait disturbance. After compatible magnetic resonance imaging (MRI), diffusion changes, and electroencephalogram (EEG) findings the case was reoriented to Creutzfeldt-Jakob disease (CJD). The genetic study found a methionine/valine heterozygosity at codon 129 of the prion protein gene PrPSc. On followup, a significant clinical recovery turned out. For this reason, EEG and MRI were repeated and confirmed the findings. The patient subsequently demonstrated progressive clinical deterioration and died 21 months later. The diagnosis was verified postmortem by neuropathology. The vCJD subtype MV2 is indeed characterized by early and prominent psychiatric symptoms and a prolonged disease duration however no frank clinical recovery has before been reported.

scholarly journals Follow-Up Investigations of Tau Protein and S-100B Levels in Cerebrospinal Fluid of Patients with Creutzfeldt-Jakob Disease

2005 ◽  
Vol 19 (5-6) ◽  
pp. 376-382 ◽  
Author(s):  
Lukas Cepek ◽  
Petra Steinacker ◽  
Brit Mollenhauer ◽  
Birgitt Wiese ◽  
Barbara Ciesielczyk ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Tau Protein ◽  
Jakob Disease

Cerebrospinal Fluid Levels of 14-3-3 Gamma: What Does It Tell Us About Sporadic Creutzfeldt-Jakob Disease?

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 243-245 ◽  
Author(s):  
Christian Humpel ◽  
Thomas Benke
Keyword(s):  
Cerebrospinal Fluid ◽  
High Risk ◽  
Retrospective Analysis ◽  
Short Report ◽  
Healthy Controls ◽  
Jakob Disease ◽  
Csf Levels ◽  
Fluid Levels ◽  
Very High ◽  
Probable Diagnosis

Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short report, we report about a retrospective analysis performed on 2,296 routinely collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075 were selected. Analysis was performed with a novel 14-3-3 gamma CircuLex Elisa. We show that control levels were around 6,000 AU/mL and samples from Alzheimer patients were not different from those collected from healthy controls. Four cases of verified CJD had 14-3-3 CSF levels of >100,000 AU/mL, while 10 out of 12 suspected CJD samples with 14-3-3 CSF levels between 50,000-100,000 AU/mL were CJD positive. All samples with 14-3-3 levels between 15,000 and 50,000 AU/mL were not CJD cases but disorders with complex neuropathology. In conclusion, our data suggests that in CSF samples with a phospho-Tau-181/Tau ratio <0.075 CSF levels of 14-3-3 should be analyzed. Our data suggests a very high risk for CJD with 14-3-3 levels above 100,000 AU/mL and a probable diagnosis of CJD based on laboratory parameters above 50,000 AU/mL.

scholarly journals Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients

Aging ◽  
2016 ◽  
Vol 8 (11) ◽  
pp. 2927-2935 ◽  
Author(s):  
Matthias Schmitz ◽  
Franc Llorens ◽  
Alexander Pracht ◽  
Tobias Thom ◽  
Ângela Correia ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Malate Dehydrogenase ◽  
Human Cerebrospinal Fluid ◽  
Jakob Disease

Decreased  -amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

Neurology ◽  
2000 ◽  
Vol 54 (5) ◽  
pp. 1099-1102 ◽  
Author(s):  
M. Otto ◽  
H. Esselmann ◽  
W. Schulz-Schaeffer ◽  
M. Neumann ◽  
A. Schroter ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Jakob Disease

scholarly journals Markers of A1 astrocytes stratify to molecular sub-types in sporadic Creutzfeldt–Jakob disease brain

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Cathryn L Ugalde ◽  
Victoria Lewis ◽  
Christiane Stehmann ◽  
Catriona A McLean ◽  
Victoria A Lawson ◽  
...  
Keyword(s):  
Functional Properties ◽  
Linear Trend ◽  
Polarization State ◽  
Reactive Astrocytes ◽  
Global Changes ◽  
Strong Linear Correlation ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Mrna Markers ◽  
Codon 129

Abstract Astrocytes are glial cells of the central nervous system that become reactive under conditions of stress. The functional properties of reactive astrocytes depend on their stimulus that induces the upregulation of specific genes. Reactive astrocytes are a neuropathological feature of prion disorders; however, their role in the disease pathogenesis is not well understood. Here, we describe our studies of one polarization state of reactive astrocytes, termed A1 astrocytes, in the frontal cortex region of 35 human sporadic Creutzfeldt–Jakob disease brains encompassing a range of molecular sub-types. Examination of two mRNA markers of A1 astrocytes, C3 and GBP2, revealed a strong linear correlation between the two following their log-normalization (P = 0.0011). Both markers were found upregulated in the sporadic Creutzfeldt–Jakob disease brain compared with age-matched control tissues (P = 0.0029 and 0.0002, for C3log and GBP2log, respectively), and stratifying samples based on codon 129 genotype revealed that C3log is highest in homozygous methionine and lowest in homozygous valine patients, which followed a linear trend (P = 0.027). Upon assessing other disease parameters, a significant positive correlation was found between GBP2log and disease duration (P = 0.031). These findings provide evidence for a divergence in the astrocytic environment amongst patients with sporadic Creutzfeldt–Jakob disease based on molecular sub-type parameters of disease. While more research will be needed to determine the global changes in the genomic profiles and resulting functional properties of reactive astrocytes in disease, considering the evidence demonstrating that A1 astrocytes harbour neurotoxic properties, the changes seen in C3log and GBP2log in the current study may reflect differences in pathogenic mechanisms amongst the sporadic Creutzfeldt–Jakob disease sub-types associated with the A1 polarization state.

scholarly journals Molecular Characterization of the Danish Prion Diseases Cohort With Special Emphasis on Rare and Unique Cases

2019 ◽  
Vol 78 (11) ◽  
pp. 980-992 ◽  
Author(s):  
Aušrinė Areškevičiūtė ◽  
Helle Broholm ◽  
Linea C Melchior ◽  
Anna Bartoletti-Stella ◽  
Piero Parchi ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Prion Disease ◽  
Prion Diseases ◽  
The Past ◽  
Disease Biology ◽  
Fresh Frozen ◽  
Jakob Disease ◽  
Disease Subtypes ◽  
Codon 129

Abstract The purpose of this study was to perform an updated reclassification of all definite prion disease cases with available fresh-frozen samples referred to the Danish Reference Center over the past 40 years, putting a special emphasis on the molecular characterization of novel disease subtypes. Investigation of the Danish prion diseases cohort revealed rare sporadic Creutzfeldt-Jakob disease cases with mixed subtypes and subtypes with previously uncharacterized white matter plaques, a new case of sporadic fatal insomnia, and 3 novel mutations, including 2 large octapeptide repeat insertions, and a point mutation in the prion protein gene. The evaluation of methionine and valine distribution at codon 129 among the prion disease patients in the cohort revealed the increased prevalence of methionine homozygotes compared to the general population. This observation was in line with the prevalence reported in other Caucasian prion disease cohort studies. Reclassification of the old prion diseases cohort revealed unique cases, the molecular characterization of which improves prion diseases classification, diagnostic accuracy, genetic counseling of affected families, and the understanding of disease biology.

Sign in / Sign up

Export Citation Format

Share Document